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The recurrence rate in patients with adenocarcinoma of the pancreas following pancreaticoduodenectomy with curative intent is > 80%

Preoperative Chemoradiotherapy increases the proportion of patients that undergo potentially curative resections for their local disease and prevents a delay in the systemic treatment of subclinical distant disease

Materials and Methods

A chemoradiotherapy regimen consisting of 7 cycles of weekly gemcitabine (400 mg/m2) with 30 Gy of radiotherapy (3 Gy / fraction) delivered in two weeks beginning 3 days after the first dose of gemcitabine was delivered in patients with biopsy proven, potentially resectable adenocarcinoma of the pancreatic head or uncinate process

Patients were re-staged with chest radiographs and CAT scans 4-6 weeks after the last chemotherapy

Those without tumor progression and good performance status underwent pancreaticoduodenectomy

The effectiveness of the preoperative therapy was evaluated on histopathologic analysis of the surgical specimen

Results

86 patients were enrolled in the trial over 3 years

All patients completed the preoperative portion of the treatment

The planned dose of radiotherapy was delivered in 100% of the patients

The planned dose of gemcitabine was delivered in 39 patients (45%)

Among patients that did not received the planned dose of gemcatibine, 23% (11/47) required a dose reduction and 77% (36/47) missed > 1 doses

37 patients (43%) required hospitalization prior to the planned surgery but no chemoradiotherapy-associated deaths were observed

Patients were restaged following chemoradiotherapy

15% of patients did not undergo surgery because of disease progression at restaging

Resection was attempted in 85%, of which 6/7th underwent a successful pancreaticoduodenectomy (this represents 73% of all patients completing the preoperative portion of the treatment) and 1/7th were found to have metastatic disease at exploration

More than 50% of tumor cells were deemed ?not viable? upon histopathologic examination in 60% of the surgical specimens

No viable tumor cells were identified in 2 (~ 3%) specimens

Author's Conclusions

Adverse effects, especially hematologic, were common but manageable

Adverse effects were attributable to the chemotherapy portion of the regimen and did not interfere with compliance of either radiotherapy or surgery

No chemoradiation-associated deaths were observed with this gemcitabine-based regimen

The rate of preoperative disease progression with this neoadjuvant therapy was low and allowed a substantial portion of the patients with pancreatic cancer to proceed to potentially curative resection

High rates of local pathologic response were observed with this gemcitabine-based chemoradiotherapy approach

Clinical/Scientific Implications

The high proportion (73%) of patients in which a successful pancreaticoduodenectomy was attained after this regimen compares favorably with other reported preoperative regimens for pancreatic cancer (~ 60%). Most patients with pancreatic cancer are seen postoperatively after a Whipple Procedure for chemoradiotherapy. Other studies are evaluating the use of Gemcytabine in the postoperative setting in association with radiation therapy.